The purpose of this study is to examine the neural basis of response inhibition, working memory, and sustained attention in adolescents and adults with Attention-Deficit/Hyperactivity Disorder (ADHD), with particular emphasis on quantifying the effects of methylphenidate (i.e., treatment with psychostimulants) on neural function. Participants will undergo electrophysiological measurement of brain function during laboratory cognitive tasks. This research is aimed to develop a better understanding of how ADHD neural dysfunction relates to clinical presentation and medication response during the transition from adolescence to adulthood. The specific aims and hypotheses are:

Specific Aim: To characterize the effect of Ritalin (methylphenidate) on neural activity underlying performance on the response inhibition task in ADHD adolescents and adults. Hypothesis 1) Methylphendiate will increase N2 and P3 amplitude in ADHD persons during medicated EEG sessions; Hypothesis 2) There will be a significant age × medication interaction such that ADHD teens will show increased amplitude of N2 while medicated, particularly at frontal sites, whereas ADHD adults will show differentially greater effect of medication on P3 amplitude and latency at central sites. Hypothesis 3) Brain activity assessed by fMRI will differ between unmedicated and medicated states.

Participants will be recruited from the community and referred from psychiatric outpatient clinics.

Criteria

Inclusion Criteria:

ADHD will be diagnosed based on DSM-IV criteria for ADHD combined subtype ADHD. Combined subtype ADHD requires at least 6 of 9 possible symptoms within both the Hyperactive-Impulsive symptom cluster and the Inattentive symptom cluster. This will be assessed using information gathered from the K-SADS-PL interview with either the potential participant or their parent, and from published self- and parent-report ADHD symptom rating scales (Brown, 1996; Barkley, 1998). Predominantly Inattentive ADHD persons will not be included. The Predominantly Inattentive subtype is the subject of much theoretical debate, as it is not clear that these persons represent a unitary disorder, or that they are neurobiologically similar to combined-subtype ADHD (Millich et al., 2001).

Exclusion Criteria:

To further aid proper ADHD diagnosis, all potential participants will be administered a battery of neuropsychological tests. Potential ADHD participants will undergo testing while unmedicated. This battery will include IQ, and attention and memory tests (WASI, Trail Making, Symbol Digit, Stroop Test, and Rey AVLT), as well as several measures of executive functioning known to be sensitive to the cognitive deficits observed in ADHD samples (Kaplan & Stevens, 2002). Normal performance on all cognitive tests known to be sensitive to ADHD will exclude participants from the study. Full Scale IQ score from the WASI below 80 or above 120 will exclude participants from further participation. Diagnostic interviews using the SCID-IV (First et al., 1996) will be used to obtain a detailed psychiatric history. Lifetime or current history of other major Axis I psychiatric disorders, including bipolar disorder, schizophrenia, substance dependence disorders, or obsessive-compulsive disorders, will exclude potential participants. These disorders may better explain the presence of attention symptomatology, which DSM-IV criteria indicate precludes an ADHD diagnosis. In addition, the disruptive behavior disorders module of the K-SADS-PL will be used to evaluate the presence of childhood Conduct Disorder and adult Antisocial Personality Disorder (ASPD). These diagnoses will also exclude further participation, as these conditions may be better associated with different abnormalities in prefrontal brain function (Bauer, 1997; Stevens et al., 2001). Potential participants also will be excluded if they report a history of head injury (e.g., loss of consciousness > 10 min), seizure disorder, life threatening disease, family history of schizophrenia, uncorrected visual or auditory deficits, or conditions contraindicated for MRI (claustrophobia, metal in body, pregnancy, etc.). Up to 25% of persons with ADHD suffer from learning disorders (Tannock & Brown, 2000). Because educational failure is so prevalent in this group, we will include these people into the study. While the strict inclusion criteria will exclude many potential participants, this is necessary to ensure a homogenous participant population that varies by the presence or absence of ADHD.

Only ADHD persons who are regularly prescribed a classic psychostimulant(Ritalin, dexedrine, etc) will be recruited. This will confirm that such persons show a beneficial therapeutic response to stimulants that can be characterized using brain function measurements. While this will prevent the comparison of brain activity response among various medications, it will simplify interpretation of the results. Finally, subjects will be excluded if they are taking any adjunctive medication for ADHD symptoms (e.g., Wellbutrin, etc.) or another psychoactive medication.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01310439